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Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis.

Dominant mutations in superoxide dismutase cause amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease that is characterized by the loss of motor neurons. Using mice carrying a deletable mutant gene, diminished mutant expression in astrocytes did not affect onset, but delayed microglial activation and sharply slowed later disease progression. These findings demonstrate that mutant astrocytes are viable targets for therapies for slowing the progression of non-cell autonomous killing of motor neurons in ALS.

Pubmed ID: 18246065

Authors

  • Yamanaka K
  • Chun SJ
  • Boillee S
  • Fujimori-Tonou N
  • Yamashita H
  • Gutmann DH
  • Takahashi R
  • Misawa H
  • Cleveland DW

Journal

Nature neuroscience

Publication Data

March 27, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS 27036
  • Agency: NINDS NIH HHS, Id: R37 NS027036
  • Agency: NINDS NIH HHS, Id: R37 NS027036-22
  • Agency: NINDS NIH HHS, Id: R37 NS027036-23

Mesh Terms

  • Amyotrophic Lateral Sclerosis
  • Animals
  • Astrocytes
  • Cell Death
  • Disease Models, Animal
  • Disease Progression
  • Genes, Dominant
  • Genetic Therapy
  • Glial Fibrillary Acidic Protein
  • Gliosis
  • Humans
  • Integrases
  • Mice
  • Mice, Transgenic
  • Microglia
  • Mutation
  • Nerve Degeneration
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Oxidative Stress
  • Spinal Cord
  • Superoxide Dismutase
  • Survival Rate